Evidence map›Paper›PMID 42481856›Full record

Observational studyPharmaceutical research2026

Integrating Clinical Evidence with PBPK Modeling to Assess PPI-Clopidogrel-CYP2C19 Interactions in Chinese ACS Patients.

Ya-Xin Liu, Yun Kuang, Jun-Long Ma, Jin-Long Liu, Nuo Xu, Qi Pei, Li-Ying Gong, Guo-Ping Yang

Abstract readObservational Study
PubMed Publisher
In one paragraph

Observational study in Pharmaceutical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ya-Xin LiuCenter of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
Yun KuangCenter of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
Jun-Long MaDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
Jin-Long LiuCenter of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
Nuo XuCenter of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
Qi PeiDepartment of Pharmacy, Central South University, The Third Xiangya Hospital, Changsha, China.
Li-Ying GongCenter of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China. gongliying2016@outlook.com.
Guo-Ping YangCenter of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China. ygp9880@126.com.ORCID http://orcid.org/0000-0001-5930-586X

Funding

Health Research Project of Hunan Provincial Health Commission W20243193National Natural Science Foundation of China 82474009Natural Science Foundation of Hunan Province 2025JJ60530
6 · The paper itself

Abstract

purposeThe interaction between proton pump inhibitors (PPIs) and clopidogrel in acute coronary syndrome (ACS) patients is mediated by CYP2C19 genetic variants. This study quantitatively assessed their CYP2C19 genotype-dependent impact on clopidogrel pharmacokinetics and pharmacodynamics using clinical data and physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling.

methodsA total of 409 ACS patients from a prospective clinical study were genotyped for CYP2C19 (*1, 2, and 3 alleles) and evaluated for platelet reactivity index (PRI) following clopidogrel therapy, with or without concomitant pantoprazole or lansoprazole use. A PBPK model was developed in PK-Sim, incorporating CYP2C19-specific metabolic pathways, and linked with a pharmacodynamic model of P2Y12 receptor inhibition to simulate the effects of genotypes and PPIs on platelet inhibition.

resultsIn extensive metabolizer individuals, PPI coadministration modestly increased platelet reactivity, while no significant change occurred in poor metabolizers. The PBPK simulations accurately predicted pharmacokinetic parameters, with over 90% of C

conclusionsThese results provide a quantitative understanding of the genotype- and PPI-dependent effects on clopidogrel's pharmacodynamics, offering a tool to personalize therapy in ACS patients.

Indexed as

Acute Coronary SyndromeClopidogrelCytochrome P-450 CYP2C19Models, BiologicalPlatelet Aggregation InhibitorsProton Pump InhibitorsTiclopidineAgedDrug InteractionsFemaleGenotypeHumansLansoprazoleMaleMiddle AgedPantoprazoleClopidogrelCYP2C19 protein, humanCytochrome P-450 CYP2C19LansoprazolePantoprazolePlatelet Aggregation InhibitorsProton Pump InhibitorsTiclopidineacute coronary syndromeantiplateletdrug-drug-gene interactionsphysiologically-based pharmacokinetic

Identifiers

PMID42481856

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.